Abstract

Purpose:

To develop a local-and-global liver function probability model to aid in physiologically adaptive RT in patients with intrahepatic cancer.

Methods:

Twenty-two patients enrolled in an IRB-approved study had liver DCE-MRI and Indocyanine green (ICG) clearance tests prior to, during and 1 month post RT. The percentage of ICG retention in the blood plasma 15 minutes after administration (ICG-R15) was used as an overall liver function measure. Portal venous perfusion images were derived from DCE-MRI. Assuming parallel architecture in the liver and considering both volume and function effects of tissue subunits, a global liver function probability Pl was assumed to be a volume-weighted summation of local function probabilities p of subunits, excluding the subunits with p<γ, a threshold indicting poor function. The local function probability p was mapped from portal venous perfusion F by a logistic function p(F)=1/(1+(F50/F)^n), where we considered function probabilities saturated at high perfusion and suppressed at low perfusion. Finally, Pl was linearly fitted to a logarithm of ICG-R15 to determine parameters (F50, n, γ). The leave-m-out technique was used to cross-validate the model. This model was applied to evaluate the doseresponse of the local function probability one month after RT.

Results:

The best fitted values of (F50, n, γ) were 65.3ml/(100g.min), 2.86 and 0.14, respectively. The leave-one-out and 10-fold tests resulted in 66.34±3.21 and 69.26±}10.35ml/(100g.min) of F50, 2.90±0.76 and 3.25±1.59 of n, and 0.14±0.03 and 0.13±}0.05 of γ, respectively. The derived Pl significantly correlated with ICG-R15 logarithm (r=0.66, P<;1e-6). Average percentage reduction in the local function probability post-RT was related to the local dose by a logistic function (P=1e−6).

Conclusion:

The local-and-global liver function probability model has the potential to guide dose redistribution during a course of treatment to spare liver functional subunits, thereby allowing target d5 ose intensification without increasing the risk for complication.